Genomic search for prostate cancer predisposition loci in Utah pedigrees

Abstract

We report a genome linkage scan in extended Utah pedigrees, utilizing a pedigree-splitting approach to reduce intra-familial heterogeneity. Fifty-nine pedigrees with at least four Prostate cancer (PrCa) cases and no more than two meioses separating PrCa cases were analyzed using the CIDR genomic search STRP marker set. Parametric linkage analyses using dominant and recessive models were performed on four datasets resulting from a pedigree splitting algorithm. In addition, age at diagnosis subset analyses were performed. Four regions of interest (LODs>1.9) were identified on chromosomes 1p, 3q, 5q, and 22q. The linkage peaks on 1p, 3q, and 22q have been previously implicated for PrCa, though not significantly. The 1p region was supported by a single large Utah pedigree with a multipoint LOD score of 3.1. An additional 10 regions gave LOD scores>1.22 (nominal linkage evidence), including moderate evidence supporting the HPC20 region with a recessive model. Our genome-wide search in the informative, extended Utah pedigrees continues to illustrate an ability to identify and replicate linkage peaks, and supports four regions of interest for PrCa predisposition genes.